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has further complicated identification of the "industrial" lead end member, because lead contamination of foods can occur during production, harvesting, storage, shipping, processing, and packaging, which can happen in different locales within a country, different countries, and even different continents.Mechanistic studies are reported on the inter- and intramolecular [2 + 2] alkene cycloadditions to form cyclobutanes promoted by (tricPDI)Fe(N2) (tricPDI = 2,6-(2,4,6-tricyclopentyl)C6H2N = CMe)2C5H3N). A combination of kinetic measurements, freeze-quench 57Fe Mössbauer and infrared spectroscopic measurements, deuterium labeling studies, natural abundance 13C KIE studies, and isolation and characterization of catalytically relevant intermediates were used to gain insight into the mechanism of both inter- and intramolecular [2 + 2] cycloaddition reactions. For the stereo- and regioselective [2 + 2] cycloaddition of 1-octene to form trans-1,2-dihexylcyclobutane, a first-order dependence on both iron complex and alkene was measured as well as an inverse dependence on N2 pressure. Both 57Fe Mössbauer and infrared spectroscopic measurements identified (tricPDI)Fe(N2)(η2-1-octene) as the catalyst resting state. Rate-determining association of 1-octene to (tricPDI)Fe(η2-1-octene) accounts for the first order dependeutane product. Despite complications from competing cyclometalation of chelate aryl substituents, deuterium labeling experiments were consistent with unimolecular C-C reductive elimination that occurred either by a concerted pathway or a radical rebound sequence that is faster than C-C bond rotation.Film-based fluorescent sensors have become an important field of sensor research due to abundant acquirable signals, real-time monitoring, and ease of miniaturization and integration, where chemically sensitive films are the most vital component of the sensor devices. In this feature article, we introduce hardware structures of film-based fluorescent sensors following the examination/investigation of the recent progress of such sensors with perylene bisimide (PBI) derivatives as sensing fluorophores in the films. PBI derivatives were specially chosen because of their outstanding chemical, photochemical, and thermal stabilities as well as their unusual high-fluorescence quantum yields. And finally, we provide a prediction for the future developments and challenges of this emerging field.A combined computational and experimental study was performed to elucidate the mechanism of the AgI-catalyzed oxidative cross-coupling/cyclization of terminal alkynes with β-enamino esters. The results indicated a more favorable AgI/Ag0-catalyzed radical mechanism (than cationic mechanism) which involves three key stages (i) the initiation of radical species, (ii) the cyclization, and (iii) the formal 1,2-H shift. Meanwhile, the AgI species was found to be the active initiator for the delocalized nitrogen radical species generation, and Ag2CO3 acts as an effective oxidant to initiate the β-enamino ester radical formation. Ivacaftor-D9 Furthermore, it was shown that the silver acetylide is the key intermediate in the title reaction and that the coordination of solvent dimethyl sulfoxide (DMSO) regulates the electronic properties of the Ag center better as compared with base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), thereby enhancing the negative charge of the reaction sites and promoting the cyclization process. Finally, the DBU was revealed to play a key role in the final 1,2-H shift process through the formation of [DBU-H]+, acting as a proton shuttle to assist the proton migration process. The theoretical results provide key insights into the AgI/Ag0-catalyzed radical mechanism and guidelines for further development of Ag-catalyzed synthetic methods.Cryo-electron microscopy (cryo-EM) has enjoyed explosive recent growth due to revolutionary advances in hardware and software, resulting in a steady stream of long-awaited, high-resolution structures with unprecedented atomic detail. With this comes an increased number of microscopes, cryo-EM facilities, and scientists eager to leverage the ability to determine protein structures without crystallization. However, numerous pitfalls and considerations beset the path toward high-resolution structures and are not necessarily obvious from literature surveys. Here, we detail the most common misconceptions when initiating a cryo-EM project and common technical hurdles, as well as their solutions, and we conclude with a vision for the future of this exciting field.Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution crystal structures of the 5-HT1B receptor with both ligands have been solved, the high similarity between these two complex structures does not sufficiently explain their activity differences and the activation mechanism of the receptor. Hence, an examination of the dynamic motion of both drugs with the receptor is required. In this study, we ran a total of 6.0 μs molecular dynamics simulations on each system. Our simulation data show the subtle variations between the two systems in terms of the ligand-receptor interactions and receptor secondary structures. More importantly, the ligand and protein root-mean-square fluctuations (RMSFs) for the two systems were distinct, with ERG having a trend of lower RMSF values, indicating it to be bound tighter to 5-HT1B with less fluctuations. The molecular mechanism-general born surface area (MM-GBSA) binding energies illustrate this further, proving ERG has an overall stronger MM-GBSA binding energy. Analysis of several different microswitches has shown that the 5-HT1B-ERG complex is in a more active conformation state than 5-HT1B-DHE, which is further supported by the dynamic network model, with reference to mutagenesis data with the critical nodes and the first three low-energy modes from the normal mode analysis. We also identify Trp3276.48 and Phe3316.52 as key residues involved in the active state 5-HT1B for both ligands. Using the detailed dynamic information from our analysis, we made predictions for possible modifications to DHE and ERG that yielded five derivatives that might have more favorable binding energies and reduced structural fluctuations.